Process for manufacture of bipyridyls

ABSTRACT

A process for the manufacture of bipyridyls which comprises heating a pyridine with 1-(4-pyridyl)-pyridinium halide at a temperature of at least 150*C.

United States Patent 11 1 1 1 3,927,009 Potter Dec. 16, 1975 PROCESS FOR MANUFACTURE OF [51] Int. Cl. C07D 213/72 BIPYRIDYLS [58] Field of Search 260/296 D [75] Inventor: glrlleglllgnigntomette Potter, Runcorn, [56] References Cited A I Ch H d t UNITED STATES PATENTS sslgnee: 'f f em'ca 2962,502 ll/l960 Hiliary et a1. 260/296 1) London England 3.040.052 6/1962 Jubb [22] Fil d; J l 1 1973 3,189,610 6/1965 Widnes 260/296 D PP 379,308 Primary ExaminerAlan L. Rotman Related US Application Data Attorney, Agent, or Firm-Cushman, Darby & [62] Division of S61. No. 171,349, Aug. 12, 1971, Pat. No. Cushman [57] ABSTRACT [30] F i A li i p i i D A process for the manufacture of bipyridyls which comprises heating a pyridine with l-(4-py1'idyl)- Aug. 17, 1970 United Kmgdom 3948i/7O pyrid nium halide at a te perat e of at ea t 150C. [52] US. Cl 260/296 D; 252/464 12 Claims, N0 Drawings PROCESS FOR, MANUFACTURE OF BIPYRIDYLS This is a division of application Ser. No. 171,349 filed Aug. 12, 1971, now US. Pat. No. 3,787,427, dated Jan. 22, 1974.

This invention relates to the manufacture of heterocyclic bases and particularlyto a process for the manufacture of bipyridyls, notably 4,4'-.bipyridyls and 2,2- bipyridyls. v A

According to the present invention we provide a process for the manufacture of bipyridyls which comprises heating a pyridine with a halogen, a 4-halopyridine or a l-(4-pyridyl)-pyridinium halide at a temperature of at least 150C.

The 4-substituted pyridine (i.e. the 4-halopyridine or the l-(4-pyridyl)-pyridinium halide), which may contain substituents for example one or more alkyl groups in addition to the 4-substituent and which may be in the form of its hydrohalide, is preferably employed in a substantially anhydrous condition. The pyridine with which the halogen or the 4-substituted pyridine is heated may be pyridine itself or a substituted pyridine, for example an alkyl substituted pyridine in which the 4-position is unsubstituted. Mixtures of a pyridine and water may be employed although such mixtures tend to result in reduced yields of bipyridyls so that a substantially anhydrous pyridine is preferred.

The temperature at which the mixture of the pyridine and the halogen or 4-substituted pyridine is heated is advantageously at least 180C although there is no ad- 2 example l-(4-pyridyl)-pyridinium chloride can be produced by reaction of pyridine or an alkyl pyridine with thionyl chloride at room temperature in known'jm'aner; this reaction is' rapid and exothermic and is accompanied by a rise in temperature of the reaction mixture but it is not generally necessary to employ cooling meansto maintain the temperature at about room temperature. Alternatively l-(4-pyridyl)-pyridinium halides can be produced in known manner by reacting pyridine or an alkyl pyridine with a halide, especially a chloride, of a metal of variable valency wherein the metal is in a higher valency state, for example tungsten hexachloride, niobium pentachloride and tantalum pentachloride. The pyridine may be heated with the metal halide at a temperature of up to 120C if necessary. It is not always necessary to isolate the pyridyl pyridinium chloride from the reaction mixture. However, we have found that higher conversions of the pyridyl pyridinium salt are obtained if it is separated prior to the conversion from any sulphur liberated during the reaction.

vantage in employing a temperature greater than 400C. The preferred temperature range is 180C to 300C. Usually the reaction will be carried out in a sealed vessel, for example a Carius tube, so that superatmospheric conditions are created when the mixture is 4-substituted pyridines for use in the process may I also be obtained by the reaction of pyridine or an alkyl ture, it may be necessary to carry out the reaction in heated. The mixture may be heated in the presence or absence of oxygen.

' The products of the process are generally mixtures of isomeric bipyridyls, notably 4,4'-bipyridyls and 2,2- bipyridyls, although we have found that the reaction conditions and notably the temperature at which and the time for which the mixture is heated'can beselected to yield a product consisting essentially of a single bipyridyl species. We have found thatin general at the lower temperatures in the range, for example about 180C, the product is essentially '4,4'-bipyridyl with traces only of other isomers, irrespective of the time of reaction. At higher temperatures, for example about 300C the initial product is again predominantly 4,4- bipyridyl but increasing the time for which the mixture is heated leads to the production of a mixture of isomeric bipyridyls and eventually to a product which contains 2,'2'-bipyridyl as the major constituent. Thus,

for example, if a mixture of 1-(4-pyridyl)-pyridinium chloride and excess pyridine is heated at 300C the product after 4 hours consists essentially of 4,4'-bipyridyl whereas the product after 10 hours consists of a mixture of 2,2'-bipyridyl, 2,4'-bipyrid'yl and 4,4- bipyridyls wherein the 2,2-bipyridyl is by far the major product. Moreover if the mixture is heated at 300C for 10 hours in the presence of an alkali-metal halide, for example potassium iodide, the product consists essentially of r2,2'-bipyr idyl and at most only traces of 4,4- bipyn'dyl are obtained. Thus the reaction can be carried out tofyield;,4;4'-bipyridyl .or 2,2'-bipyridyl substantially free from other isomeric bipyridyls.

' The -4-substituted pyridines'for use in the process of the invention can be pro'du'eed, in a variety of ways. For

the presence of a Friedel Crafts catalyst for example aluminium trichloride or ferric chloride. The resulting l-(4-pyridyl)-pyridinium salt may be converted to bipyridyls without isolation from the reaction mixture. Indeed the pyridine and the halogen may be heated initially at a temperature of greater than C so that bipyridyls are obtained directly and this technique is a preferred embodiment of the invention. In this embodiment-it is believed that a 4-substituted pyridine as hereinbefore defined may be formed as an intermediate species but the mechanism of the reaction is not fully understood and the invention is in no way limited by any particular theory.

The reaction between the pyridine and the halogen may be carried out by heating a'solution of the halogen in the pyridine. We have found that in general reaction of the pyridine and the halogen is favoured by temperatures in excess of 200C, for example about 300C and that at these higher temperatures the product tends to contain mixed isomers, of which 2,2'-bipyridyls are the major constituents. However, at lower temperatures, for example about 180C, the product contains a 4,4- bipyridyl as the major constituent. Moreover, if a pyridine and bromine are heated in the presence of palladium bromide, the product is essentially the 2,2- bipyridyl, irrespective of time and temperature.

The bipyridyls can be isolated from the reaction mixture in which theyare formed by conventional methods, for example by adding an aqueous" solution of a base, notably sodium hydroxide, followed bysolvent extraction of the resulting basic. mixture, using for ex- 3 chromatography.

The bipyridyls are useful for conversion by quaternisation for example by means of an alkyl halide into N,N'-disubstituted-bipyridylium salts which are useful nets are shown in Table l, in which PPC represents 1- (4-pyridyl)-pyridinium chloride and PPCHCI its hydrochloride.

EXAMPLES 15-25 herbicides.

The invention is illustrated but 11'] no way limited by These examples demonstrate the conversion of 4- the following examples wherein yields of products are halopyridines to bipyridyls. based on 4-substituted pyridine fed unless otherwise The experimental procedure was the same as de- Staiedt scribed in Examples 1-14 but using a 4 -halopyridine instead of pyridyl pyridmium chloride.

Table l Example PPC or mls metal or Temp Time Products PPCHCl pyridine metal salt (C) (hrs) Bipyridyls l PPC l 300 I0 2,2'(25) 4,4'( 13) 2,4'( l-2) 2 PPC.HCl 6 I80 4 4,4'(l7.4)

2,4'-( l) 3 PPC.HCl l0 I80 4 4,4'(ll.3) 4 PPC 6 180 4 4.4'(l 1.8) 5 PPCHCI 6 180 4 4,4'(l5.3)

(ultrapure) 6 PPC 6 250 4 4,4'( 7 PPC 6 mls of 180 4 4,4'-(7.75)

aqueous pyridine (H 0=30%) 8 PPCHCI 6 mls of l80 4 4,4'(6.l5)

aqueous pyridine 30% H 0) 9 PPC 6 l 10 No bipyridyls l0 PPC 7 FeSO. 180 4 4,4'(5.6)

1.44 ll PPC 7 CaCl I80 4 4,4'(4.8)

(0.51) 12 PPC 7 I K] 300 I0 2,2'(l7.5)

(0.95) (No 4,4'-) 13 PPC 7 Zn (0.2) 180 4 4,4'(6) l4 PPC 7 mls of Zn (0.2) 180 4 4,4'(5) aqueous pyridine H O) Table 11 Ex. Substituted Pyridine Mls Temp Time Products No. Pyridine (C) (Hrs) l5 4-brornopyridine.HCl 5 250 4 4,4'( 44.5) 16 4-bromopyn'dine.HCl 6 I 80 4 4,4'(6 l .5) l7 4-brornopyridine.HCl 3.5g H30 5 4.4'--( l0) l8 4chloropyridine.HCl 6 l 4,4'( 26) 19 4-brom0pyridine.HCl 6 l 60 4,4'( 26.7) 20 4-bromopyridine 6 l 4 4,4'(46.S) 2 l 4-bromopyridine,HCl 6 I80 4 4,4'-( 62) 22 4-bromopyridine.HCl 2.5 300 4 (2.2( 15) (2,4'( 24) (4,4(2l 23 4-chloropyridineiHCl 6 180 4 4,4'-( 54) 24 4-bromopyridine.HCl 6 5 (PPC (63) (No bipyridyls) 25 4-bromopyridine.HCl 6 6O 2 PPC (17.3)

*pyridincHCl used instead of pyridine.

EXAMPLES l-l4 EXAMPLES 26-46 These examples illustrate the production of 4,4- bipyridyls and 2,2-bipyridyls from pyridine and halogen.

The experimental procedure was as follows, details of amounts of reagents, temperature and time being shown in Table III, in which Products indicates the yield of bipyridyl basedon halogen fed.

A. Halogen Chlorine A solution of chlorine in pyridine was prepared by passing chlorine in a stream of nitrogen through pyridine at a temperature of 0C. A portion of the solution was transferred under an atmosphere of nitrogen to a reaction mixture was treated and analysed as described above.

in the presence of pyIidineHCI (lg) "a solution of chlorine in pyridine was employed Carius tube which was then sealed and heated to the required temperature at which it was maintained for the desired period of time. 7

The tube was then cooled to room temperature and its content filtered. The solid was dissolved in a mixture of methanol and aqueous ammonia and the resulting solution was analysed by gas/liquid chromatography. B. Halogen Bromine or Iodine Pyridine was placed in a Carius tube and its temperature was reduced to 0C. The halogen was slowly added in the required amount and then the Carius tube was frozen, evacuated, sealed and then heated at the desired temperature for the required period of time. The

EXAMPLES 47-68 Pyridine (14 ml) was placed in a Carius tube and its temperature was reduced to 0C. Bromine"(0.8 ml) was added slowly in the desired amount and where appropriate (see Table below) a metal salt also was added. The contents of the tube were frozen and the tube was then evacuated and sealed. The contents of the tube were then heated at the temperature and for the time shown in the Table below. The resulting mixture was cooled to room temperature and filtered and the solid residue was dissolved in a mixture of methanol and aqueous ammonia. The resulting solution was analysed for bipyridyls by gas/liquid chromatography.

Table IV Temp Time Pyridine Yield 4,6'bipyridyl Example Additive (C) (Hrs) Consumed Pyridine on Bromine 47 l 80 4 14 3 9 3 3 48 200 4 20 44 52 49 AlCl lg) 220 4 13 47 50 220 4 l0 8 7 52 5 l 240 4 2 l 3 8 46 52 l 4 20 l 6 l9 5 3 26,0 4 l 8 42 46 54 220 4 l4 4 8 38 5 5 220 4 l 3 7 0 5 2 56 220 4 l 5 5 2 45 Table lV-continued Temp Time Pyridine Yield 4.6-bipyridyl Example Additive (C) (Hrs) Consumed Pyridine on Bromine 57 CuBr (0.Zg) 220 4 l4 6i 52 S8 220 IO 63 53 59 220 4 32 55 52 60 AlCl -,(().3g) 220 4 35 24 5O 6] 220 4 l l 88 56 *62 220 4 52 34 35 "63 C H.;(7 ml) 220 4 35 34 35 64 220 4 18 42 45 65 220 4 l() 50 59 "66 220 4 27 49 40 67 220 2 24 24 35 68 220 l 14 34 28 amount bromine increased to 2.4 ml "amount pyridine reduced to 7 ml ""amount bromine increased to 1.6 ml

7. A process as claimed in claim 6 wherein the alkalimetal halide is potassium iodide.

l claim:

1. A process for the manufacture of a 2,2'-bipyridyl, a 2,4'-bipyridyl or a 4,4'-bipyn'dyl which consists essentially of heating pyridine in the liquid phase under substantially anhydrous conditions with a member selected from the group consisting of a l-(4-pyridyl)- pyridinium halide and the hydrohalide addition salts thereof at a temperature of at least l50C and up to 400C.

2. A process as claimed in claim 1 wherein the temperature is from l80C to 300C.

3. A process as claimed in claim 1 which is carried out under superatmospheric pressure.

4. A process as claimed in claim 3 which is carried out in a sealed vessel.

5. A process as claimedin claim 1 wherein the temperature is at least 200C.

6. A process as claimed in claim 1 wherein the pyridine and the l-(4-pyridyl)-pyridinium halide are heated in the presence of an alkali-metal halide.

8. A process as claimed in claim 1 wherein the hydrochloride is employed.

9. A process as claimed in claim 1 wherein a 1-(4- pyridyl)-pyridinium chloride is employed which is obtained by reacting a pyridine with thi'onyl chloride.

10. A process as claimed in claim 9 wherein the l-(4- pyridyl)-pyridinium chloride is separated from sulphur prior to heating it with pyridine. 7

11. A process as claimed in claim 1 wherein a l-(4- pyridinium halide is employed which is obtained by heating a pyridine at below 120C with a member selected from the group consisting of tungsten hexachloride, niobium pentachloride and tantalum pentachloride.

12. A process as claimed in claim 1 wherein the l-(4- pyridyl)-pyridinium halide is obtained by reacting a pyridine with a halide of a metal of the B-sub Groups of Groups III to V of the Periodic Table according to Mendeleeff. 

1. A PROCESS FOR THE MANUFACTURE OF A 2,2''-BIPYRIDYL, A 2,4''-BIPYRIDYL OR A 4,4''-BIPYRIDYL WHICH CONSISTS ESSENTIALLY OF HEATING PYRIDINE IN THE LIQUID PHASE UNDER SUBSTANTIALLY ANHYDROUS CONDITIONS WITH A MEMBER SELECTED FROM THE GROUP CONSISTING OF A 1-(4-PYRIDYL)-PYRIDINIUM HALIDE AND THE HYDROHALIDE ADDITION SALTS THEREOF AT A TEMPERATURE OF AT LEAST 150*C AND UP TO 400*C.
 2. A process as claimed in claim 1 wherein the temperature is from 180*C to 300*C.
 3. A process as claimed in claim 1 which is carried out under superatmospheric pressure.
 4. A process as claimed in claim 3 which is carried out in a sealed vessel.
 5. A process as claimed in claim 1 wherein the temperature is at least 200*C.
 6. A process as claimed in claim 1 wherein the pyridine and the 1-(4-pyridyl)-pyridinium halide are heated in the presence of an alkali-metal halide.
 7. A process as claimed in claim 6 wherein the alkali-metal halide is potassium iodide.
 8. A process as claimed in claim 1 wherein the hydrochloride is employed.
 9. A process as claimed in claim 1 wherein a 1-(4-pyridyl)-pyridinium chloride is employed which is obtained by reacting a pyridine with thionyl chloride.
 10. A process as claimed in claim 9 wherein the 1-(4-pyridyl)-pyridinium chloride is separated from sulphur prior to heating it with pyridine.
 11. A process as claimed in claim 1 wherein a 1-(4-pyridinium halide is employed which is obtained by heating a pyridine at below 120*C with a member selected from the group consisting of tungsten hexachloride, niobium pentachloride and tantalum pentachloride.
 12. A process as claimed in claim 1 wherein the 1-(4-pyridyl)-pyridinium halide is obtained by reacting a pyridine with a halide of a metal of the B-sub Groups of Groups III to V of the Periodic Table according to Mendeleeff. 